Sodium Hydroxide → (R)-2-(9-chloro-7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acid

HRID 1526418Notes

Reaction equation

HRID 1526418 reaction equation
[Cl:1][C:2]1[C:10]2[CH:9]=[C:8]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][CH:20]([CH3:22])[CH3:21])=[C:15]([C:23]([F:26])([F:25])[F:24])[CH:14]=3)[CH:7]=[CH:6][C:5]=2[N:4]2[CH2:27][CH2:28][C@H:29]([CH2:30][C:31]([O:33]CC)=[O:32])[C:3]=12.[OH-].[Na+]>O1CCOCC1.CO>[Cl:1][C:2]1[C:10]2[CH:9]=[C:8]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][CH:20]([CH3:22])[CH3:21])=[C:15]([C:23]([F:24])([F:25])[F:26])[CH:14]=3)[CH:7]=[CH:6][C:5]=2[N:4]2[CH2:27][CH2:28][C@H:29]([CH2:30][C:31]([OH:33])=[O:32])[C:3]=12

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 68240766(R)-ethyl 2-(9-chloro-7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

Product 1

HCID 53362086(R)-2-(9-chloro-7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acidYield 94.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (R)-ethyl 2-(9-chloro-7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (54.6 g, 107 mmol) in dioxane (750 mL) and MeOH (75 mL) was added NaOH (aq. 3N, 89.0 mL, 268 mmol). The mixture was stirred at room temperature for 17 h, concentrated in vacuo to approx 150 mL, and acidified with aqueous 3N HCl (300 mL). The resulting slurry was shaken and the solid filtered, washed with H2O (twice), hexanes and dried in a vacuum oven (50° C., 2 Torr, 15 h) to give (R)-2-(9-chloro-7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acid (51.3 g, 101 mmol, 94% yield, >98% ee) as a white solid. Exact mass calculated for C24H23ClF3NO4: 481.1, found: LCMS m/z=482.2, [M+H+]; 1H NMR (400 MHz, CD3CN) δ ppm 1.33 (d, J=6.0 Hz, 6 H), 2.34 (m, 1 H), 2.58 (dd, J1=16.5, J2=9.7 Hz, 1 H), 2.86 (m, 1 H), 3.06 (dd, J1=16.5, J2=4.2 Hz, 1 H), 3.73 (m, 1 H), 4.01 (m, 1 H), 4.14 (ddd, J1=9.9, J2=8.5 Hz, J3=4.9 Hz 1 H), 4.75 (sep, J=6.0 Hz, 1 H), 5.08 (s, 2 H), 6.87 (dd, J1=8.8, J2=2.4 Hz, 1 H), 7.01 (d, J=2.4 Hz, 1 H), 7.18 (d, J=8.6 Hz, 1 H), 7.21 (d, J=8.8 Hz, 1 H), 7.63 (dd, J1=8.6, J2=2.1 Hz, 1 H), 7.68 (d, J=2.1 Hz, 1 H), 9.10 (bs, 1 H).

Workup

  1. concentrationconcentrated in vacuo to approx 150 mL
  2. stirringThe resulting slurry was shaken
  3. filtrationthe solid filtered
  4. washwashed with H2O (twice), hexanes
  5. customdried in a vacuum oven (50° C., 2 Torr, 15 h)

Sources & evidence

ORD record
ord-526ea5fd9b8d4de791b3c2deff4b40e8
Source dataset
uspto-grants-2015_07
Patent number
US09085581B2

Reaction notes

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